Se cond Cancers and Residual Disease in Patients Treated for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma by

Helicobacter pylori Eradication and Followed for 10 Years

Gastroenterology, Volume 143, Issue 4, October 2012, Pages e13-e14

By:azadbakht

• Development of gastric mucosa-associated lymphoid tissue (MALT) and gastric MALT lymphoma (GML) is closely linked to Helicobacter pylori infection.

• Cure of Helicobacter pylori infection induces remission in most patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) that is associated with these bacteria.

• Eradication of the bacterium has been established as the first-choice treatment option for H pylori–positive, early-stage GML.

• This prospective, multicenter trial included 120 patients (63 female, 57 male) with a mean age of 62 (range, 29–88) years.

• All patients with positive stage EI1 GML according to the Ann Arbor system, as modified by Musshoff and Radaszkiewicz, where lymphoma is limited to the mucosa and submucosa of the stomach with no lymph node involvement, were eligible for this study.

• Staging procedures included a clinical examination, full blood count, biochemistry, abdominal ultrasound, imaging of chest and abdomen by computed tomography scan, and endoscopic ultrasound.

• Presence of H pylori was demonstrated by Warthin-Starry staining.

• Treatment of study patients involved a 2-week course of amoxicillin (3 × 750 mg daily) and omeprazole (3 × 40 mg daily). Second-line treatment consisted of a triple regimen containing omeprazole (2 × 20 mg daily), metronidazole (3 × 400 mg daily), and clarithromycin (2 × 250 mg daily) for 10 days.

• Diagnostic criteria for GML were unequivocal evidence of lymphoepithelial destruction and replacement of gastric glands by uniform centrocyte-like cells.

• Histologic analysis was the standard for assessing remission status.

• Lymphoid infiltrate in post-treatment biopsies revealing monotonous infiltrates of centrocyte-like cells and/or lymphoepithelial lesions was considered histologic residual lymphoma.

• Initially, endoscopic controls were carried out at monthly intervals. After CR, endoscopic controls were continued every 6 to 12 months.

• Second cancers were documented during follow-up.

• as relapse, when macroscopic and microscopic evidence of lymphoma was present.

• A watch-and-wait strategy was used for patients with histologic residual disease .

• Kaplan–Meier analysis was used to estimate survival and remission duration.

• In 96 of 120 patients (80%), first CR was reached between 1 and 28 months after the start of eradication of H pylori.

• Median age at the last follow-up was 73 years (range, 38–89 years).

• Estimated mean survival time was 147 months (95% CI, 138–156 months). Estimated percentage of patients surviving at least 5 years was 89.4% (95% CI, 83.7–95.1), with 81.7% (95% CI, 74.1–89.2) surviving at least 10 years (Kaplan–Meier analysis).

• Median follow-up of the 96 complete responders was 126 (range, 8–171) months. The 5-year survival rate was 94% and the 10-year survival rate was 87%. Median endoscopic follow-up was 79 (range, 4–168) months.

• Of the 96 complete responders, 15 died at a median age of 70 years (range, 52–83 years) after a median follow-up of 89 months (range, 8–164 months). Causes of death were reported by the treating physicians as follows: cerebral hemorrhage (n = 1); colorectal cancer (n = 2); gastric cancer (n = 2); myocardial infarction (n = 3); heart failure (n = 2); stroke (n = 1); unknown (n = 3); lung cancer (n = 1). No patient died of GML.

• A total of 24 of the 120 patients (20%) died during the study period, 9 of which were nonresponders. Causes of death in the nonresponders were as follows: T-cell-derived non-Hodgkin lymphoma (NHL; n = 1), diffuse large B-cell lymphoma (n = 2), gastric cancer (n = 1), stroke (n = 2); heart failure (n = 2); and unknown (n = 1).

• Histologic residual disease was observed in 16 of 96 (17%) patients after a median CR of 48 months (range, 3–68 months)

• all but one patient with histologic residual disease showed CR at the last time point, with a median CR duration of 46 months (range, 0–158 months).

• A macroscopic relapse was diagnosed in 3 of 96 (3%) H pylori–negative patients within 4, 5, and 24 months of lymphoma remission. These patients were referred for alternative treatment, namely surgery (n = 2) or radiotherapy (n = 1).

• Eight patients had a history of malignancies before the diagnosis of GML, and 3 of these had been diagnosed with Hodgkin lymphoma.

.During follow-up, additional second cancers were diagnosed in the 96 complete responders . Among these were 7 cases of NHL.

• Second gastric cancers were diagnosed in 5 patients in CR.

• The risk of gastric cancer and NHL was especially high: morbidity ratio was 8.567 (95% CI, 3.566–20.582; P < .001) for gastric cancer and 18.621 (95% CI, 8.365–41.448; P < 10−6) for NHL.

• Several studies have shown that 55%–94.7% of patients with early-stage GML experience remission after H pylori eradication. The remission rate of 80% in the 120 GML patients in this study is in line with these findings.

• Long-term stable remission was found in the majority of patients, and H pylori eradication was the accepted standard therapy in patients with H pylori–positive localized GML.

• The deaths that occurred in this study were unrelated to GML; thus, GML survival rate is even higher.

• we believe that our data and the findings of Capelle et al show that GML patients are at a higher risk for second gastric cancer.

• Histologic residual disease and ongoing B-cell clonality were present in a considerable number of patients. Due to the indolent course of the disease, a watch-and-wait strategy seems to be justified in these patients.

• A total of 66 patients were investigated previously for t(11;18). Patients with translocation t(11;18) (n = 10/66) were significantly more likely to experience worse clinical outcomes (eg, partial remission, no change, relapse, or histologic residual disease), while patients without translocation t(11;18) (n = 56/66) were more likely to remain in continuous complete remission (CR) (P = .007; 95% CI, 1.47–5.63).

• Follow-up of the 3 patients with t(11;18) who achieved CR showed that they were in ongoing continuous CR for 12, 39, and 165 months.

• The translocation t(11;18) occurs in 24%–48% of GMLs and is associated with resistant disease. This is in line with our finding of 30% continuous CR in patients with t(11;18). H pylori eradication is a reasonable first-line treatment in these patients, too, especially because there are reports that t(11;18)-positive GMLs have an indolent clinical course.